Manol Jovani

Global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion

Cirrhosis presents with variable degrees of thrombocytopenia that might cause bleeding during invasive procedures. Transfusion of one standard adult platelet dose is often employed to prevent bleeding in thrombocytopenia, but the threshold platelet count that is clinically effective is not well established because clinical studies and laboratory tools to judge on efficacy are insufficient. However, in vitro studies showed that patients with cirrhosis generate as much thrombin as healthy individuals provided that their platelet count is at least 100 × 109/L.

Advances, problems, and complications of polypectomy

The major role of colonoscopy with polypectomy in reducing the incidence of and mortality from colorectal cancer has been firmly established. Yet there is cause to be uneasy. One of the most striking recent findings is that there is an alarmingly high incomplete polyp removal rate. This phenomenon, together with missed polyps during screening colonoscopy, is thought to be responsible for the majority of interval cancers. Knowledge of serrated polyps needs to broaden as well, since they are quite often missed or incompletely removed. Removal of small and diminutive polyps is almost devoid of complications. Cold snare polypectomy seems to be the best approach for these lesions, with biopsy forcep removal reserved only for the tiniest of polyps. Hot snare or hot biopsy forcep removal of these lesions is no longer recommended. Endoscopic mucosal resection and endoscopic submucosal dissection have proven to be effective in the removal of large colorectal lesions, avoiding surgery in the majority of patients, with acceptably low complication rates. Variants of these approaches, as well as new hybrid techniques, are being currently tested. In this paper, we review the current status of the different approaches in removing polypoid and nonpolypoid lesions of the colon, their complications, and future directions in the prevention of colorectal cancer.

Anti-IL-6 treatment for inflammatory bowel diseases: next cytokine, next target.

Inflammatory bowel diseases (IBD) are chronic, relapsing, and destructive inflammatory disorders of the gastrointestinal tract. Both Crohns disease (CD) and ulcerative colitis (UC) seem to arise from an impaired dialog between the environment and gut microbiota in genetically susceptible hosts, leading to an inappropriate immune activation and resulting in the over-production of pro-inflammatory cytokines. IL-6 is a key modulator of inflammatory response. It is a phylogenetically important cytokine with relevance in IBD, as well as in other chronic inflammatory diseases and cancer. Influencing the production of this cytokine can change the balance of effector CD4+ T cell subsets and induce B cell antibody production. Moreover, given IL-6 is mostly produced from innate immune cells such as macrophages, neutrophils and mast cells, it is a strategic bridge between the innate and the adaptive system. Interestingly, IL-6 induced signaling can be primarily seen in a relatively small number of IL-6 responsive cells whereas in a chronic phase of inflammation it is able to activate almost all cells of the body through a process known as trans-signaling. In this review, we discuss the role of IL-6 in chronic inflammation, with particular emphasis on its role in CD and UC, and we explore the potential to develop anti-IL-6 agents for IBD treatment.

Vedolizumab for the Treatment of IBD: A Selective Therapeutic Approach Targeting Pathogenic a4b7 Cells

Inflammatory bowel diseases (IBD) are characterized by a persistent recruitment of large quantities of leucocytes from the blood to the gut mucosa. Adhesion molecules, such as integrins and their ligands, are the main players in this complex process. Leucocyte traffic control using a specific integrin inhibitors, such as natalizumab, has been plagued by severe systemic effects. The α4β7 - integrin and its ligand, the MadCAM-1, have been of special interest, since they are found exclusively on the gut-homing lymphocyte subpopulations and in the intestinal mucosa respectively. It follows that inhibition of such molecules should offer gut-specific immunosuppression, without the systemic effects of aspecific integrin- antagonists. We review the role of vedolizumab, a humanized antibody against the α4β7 - integrin, in both ulcerative colitis (UC) and Crohns disease (CD). Results from clinical trials show that vedolizumab is effective in the induction and maintenance of remission in active CD and UC and has a very good safety profile. These data allow to confidently prospect that vedolizumab will be an important therapeutic option in the future of IBD treatment.

Review article: optimal preparation for surgery in Crohn's disease

One‐third of Crohns disease (CD) patients will undergo abdominal surgery within the first 5 years of diagnosis.

The long-term benefits of nucleos(t)ide analogs in compensated HBV cirrhotic patients with no or small esophageal varices: A 12-year prospective cohort study.

BACKGROUND & AIMS Esophageal varices (EV) are a marker of disease severity in compensated cirrhosis due to hepatitis B virus (HBV) which predicts also the risk of hepatocellular carcinoma (HCC), clinical decompensation and anticipated liver related death. The dynamics and prognostic significance of EV in patients under long-term HBV suppression by nucleos(t)ide analogs (NUC), are poorly known. METHODS A standardized protocol (Baveno) including 414 upper gastrointestinal (GI) endoscopies was applied to 107 HBeAg-negative compensated cirrhotic patients (93% Child-Pugh A) during a median of 12 (range 2 to 17) years of NUC therapy. Patients who initially started on lamivudine (LMV) and then developed resistance (LMV-R), were rescued by early administration of adefovir, or were switched to tenofovir. Surveillance included serum HBV DNA every three months and abdominal ultrasound every six months. RESULTS Twenty-seven patients had baseline F1 EV which regressed in 18, remained unchanged in eight and progressed in one patient; the 12-year cumulative incidence of EV regression was 83% (95% CI: 52-92%). De novo F1/F2 EV developed in 6/80 patients with a 12-year cumulative incidence of 10% (95% CI: 5-20%). Six of seven patients with de novo varices or progression of pre-existing varices had either a clinical breakthrough due to LMV-R and/or developed a HCC. No bleedings from ruptured EV occurred, 12 patients died (9 HCC) and 15 were transplanted (13 HCC): the 12-year cumulative incidence of HCC and overall survival was 33% (95% CI: 24-42%) and 76% (95% CI: 67-83%), respectively. CONCLUSIONS Long-term pharmacological suppression of HBV in HBeAg-seronegative patients with compensated cirrhosis leads to a significant regression of pre-existing EV accompanied by a negligible risk of developing de novo EV.

Anti-IL-13 in inflammatory bowel disease: from the bench to the bedside.

Much work has been done to understand the molecular mechanisms underlying the inflammatory bowel diseases (IBD). IL-13 has emerged as an important cytokine effective in ulcerative colitis (UC) and fistulizing Crohns disease (CD). IL-13 is a T helper 2-type cytokine with pleiotropic effects, involved in parasite expulsion, asthma pathophysiology, natural history of cancer and other human pathologies. Great interest has therefore been developed in inhibiting its function as a therapeutic intervention in these diseases. The multifunctional properties of IL-13, with particular emphasis on its role in both CD and UC, as well as current developing pharmacologic agents inhibiting the IL-13 signaling pathway have been reviewed. Anti-IL-13 agents seem to be promising therapeutic strategies for the future management of IBD and other human diseases.

Endo-sponge therapy for management of anastomotic leakages after colorectal surgery: A case series and review of literature

BACKGROUND Endo-sponge treatment is a novel approach to manage selected patients with anastomotic leakage following colorectal surgery. However, the available data are still scanty. AIMS To evaluate the efficacy and safety of the endo-sponge therapy in a large series, and to perform a review of the current evidence concerning such a treatment. METHODS Consecutive patients diagnosed with partial colonic anastomotic leakage managed with endo-sponge placement were enrolled. The endo-sponge system was changed every 48-72 h as outpatient, until to cavity closure. Literature review was performed for pooled-data analysis. RESULTS Twenty-five patients were enrolled, including 13 (52%) with diverting ileostomy. Following endo-sponge applications (median sessions: 9, range: 1-39; median treatment duration: 4 weeks, range: 1-32), a complete healing was achieved in 22 (88%) patients. Three (12%) patients developed a major complication (1 uretheric fistula, 1 ileal fistula, and 1 pararectal abscess), all successfully treated by surgery. Ileostomy closure was achieved in 11 (84.6%) patients. No mortality related to the procedure was observed. Overall, 174 patients treated with endo-sponge were reported in literature. By considering data of the larger 7 studies, a complete healing of presacral cavity was achieved in 131 (94.3%) out of 149 patients. CONCLUSIONS Our relatively large series of patients confirmed the efficacy, tolerability, and an acceptably low complication rate of endo-sponge therapy for colorectal anastomosis leakage treatment.

Novel fork-tip needles versus standard needles for EUS-guided tissue acquisition from solid masses of the upper GI tract: a matched cohort study

Abstract Background: There are very few available data on the novel SharkCore™ needles for EUS-FNB. Aim: Comparison of the performance of the SharkCore™ needles with the standard EUS-FNA needles for the diagnosis of solid upper GI masses. Patients and methods: Single-center, retrospective cohort study in an academic tertiary referral hospital. Patients were matched 1:1 for the site of the lesion and the presence or absence of rapid on-site evaluation (ROSE). Results: A total of 102 patients were included. There was no statistically significant difference in the mean number of passes (3.3 ± 1.3 versus 3.4 ± 1.5; p = .89). Similar results were observed at the subgroup with ROSE (4.3 ± 1.3 versus 3.7 ± 1.5; p = .26). More histological specimens were obtained with the SharkCore™ needles compared to standard needles (59 versus 5%; p < .001). Diagnostic test characteristics were not significantly different (sensitivity: 91.5 versus 85.7; specificity: 100 versus 100%; accuracy: 92.2 versus 85.4% for SharkCore™ versus standard needles, p > .05 in all cases). At multivariable analysis, there was no statistically significant difference in the mean number of passes in all patients (p = .23) and in the ROSE subgroup (p = .66). However, the SharkCore™ needle obtained significantly more histological material than the standard needle (odds ratio 66; 95% confidence interval: 11.8, 375.8, p < .001). There was no significant difference in complication rates (p = .5). Limitations: Retrospective study, single-center. Conclusion: The SharkCore needles were similar to standard FNA needles in terms of the number of passes to reach diagnosis, but obtained significantly more histological specimen.

International Intraductal Papillary Mucinous Neoplasms Registry: Long-Term Results Based on the New Guidelines

Objective The aim of this study was to analyze the outcomes of a long-term intraductal papillary mucinous neoplasm (IPMN) registry and evaluate new guidelines. Methods A prospectively maintained IPMN registry involving 6 centers in Europe and the United States was used to collect the data. Patients with more than 1-year follow-up and no malignancy diagnosed within the first 3 months of surveillance were included. Results From 1999 to 2014, 620 patients were included. The median follow-up time was 3 years. Thirty-seven (6%) patients developed malignancy with a median time from IPMN diagnosis to malignancy of 10.3 months. The 1-, 5-, and 10-year actuarial rates of disease-free survival were 97%, 93%, and 92% respectively. Four hundred thirty-one patients met criteria for low-risk branch duct IPMN consisting of cyst size less than 3 cm, with no solid component or main duct dilation. Eight malignancies were diagnosed in this subgroup, all of them within the first 5 years. From this subcohort, 112 patients had a follow-up time of more than 5 years, and no malignancy was diagnosed. Conclusions In IPMN lesions with low-risk features at baseline, the risk of progression to malignancy after the first 5 years of follow-up was minimal. Furthermore, the main cyst characteristics remained unchanged during their surveillance.